In:
Genes & Development, Cold Spring Harbor Laboratory, Vol. 16, No. 4 ( 2002-02-15), p. 439-451
Abstract:
β-TrCP/E3RS (E3RS) is the F-box protein that functions as the receptor subunit of the SCF β-TrCP ubiquitin ligase (E3). Surprisingly, although its two recognized substrates, IκBα and β-catenin, are present in the cytoplasm, we have found that E3RS is located predominantly in the nucleus. Here we report the isolation of the major E3RS-associated protein, hnRNP-U, an abundant nuclear phosphoprotein. This protein occupies E3RS in a specific and stoichiometric manner, stabilizes the E3 component, and is likely responsible for its nuclear localization. hnRNP-U binding was abolished by competition with a pIκBα peptide, or by a specific point mutation in the E3RS WD region, indicating an E3–substrate-type interaction. However, unlike pIκBα, which is targeted by SCF β-TrCP for degradation, the E3-bound hnRNP-U is stable and is, therefore, a pseudosubstrate. Consequently, hnRNP-U engages a highly neddylated active SCF β-TrCP , which dissociates in the presence of a high-affinity substrate, resulting in ubiquitination of the latter. Our study points to a novel regulatory mechanism, which secures the localization, stability, substrate binding threshold, and efficacy of a specific protein-ubiquitin ligase.
Type of Medium:
Online Resource
ISSN:
0890-9369
,
1549-5477
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2002
detail.hit.zdb_id:
1467414-2
SSG:
12
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